Malignant melanoma - An update

Context.-The rapidly developing fields of melanoma research are revolutioni zing the current concepts on melanoma etiology and pathogenesis and are int roducing newer diagnostic techniques and potential therapeutic approaches. Objectives.-To present the most current concepts on the etiology and pathog enesis of melanoma and to introduce the recent diagnostic techniques and th e potential therapeutic approaches. Methods.-Data sources were reports on melanoma published in the English lan guage literature and observations made using specimens available at Harvard University, Johns Hopkins Medical Center, Albany Medical College, Loyola U niversity Medical Center, and University of Tennessee Health Science Center . Results.-Studies on melanoma containing chromosomal or genetic evaluation w ere selected for further analysis. Current clinical and pathologic categori es with the reported genetic abnormalities were related to the latest infor mation on pigment biology. The data extracted were used to develop a concep tual framework on the pathogenesis of melanoma; the generated model was the n evaluated and used to suggest potential therapeutic approaches. Conclusions.-(1) Melanoma is not genetically homogenous, and the existing d ifferences between the pathologic categories, particularly in areas such as type of growth phase (radial vs vertical growth), total vertical dimension , ulceration of primary tumor, and metastatic process, have profound progno stic and therapeutic implications. (2) Chromosomal aberrations and gene mut ations are found in sporadic and familial melanomas; among the most importa nt are those affecting the 9p21, which contains the p16 locus, a site known to be critical for normal progression of the cell cycle. Aberrant p16 expr ession is associated with more aggressive behavior. (3) Melanoma cells poss ess a remarkable repertoire of biosynthetic capacities represented by the p roduction of hormones, growth factors, and their receptors that may sustain and accelerate tumor development and progression. For example, expression of the tumoral products alpha -melanocyte-stimulating hormone and adrenocor ticotropic hormone is regulated in vitro by ultraviolet light, a known carc inogen. (4) Melanomas differ from other tumors in their intrinsic capabilit y to express melanogenic enzymes with the corresponding structural proteins to actually synthesize melanin. Melanogenesis-related proteins are rapidly entering the clinical arena, being used not only as diagnostic markers, bu t also as potential targets for melanoma therapy.